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Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer
Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protop...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028356/ https://www.ncbi.nlm.nih.gov/pubmed/35456936 http://dx.doi.org/10.3390/ijms23084117 |
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author | Mossakowska, Beata Joanna Shahmoradi Ghahe, Somayeh Cysewski, Dominik Fabisiewicz, Anna Tudek, Barbara Siedlecki, Janusz Aleksander |
author_facet | Mossakowska, Beata Joanna Shahmoradi Ghahe, Somayeh Cysewski, Dominik Fabisiewicz, Anna Tudek, Barbara Siedlecki, Janusz Aleksander |
author_sort | Mossakowska, Beata Joanna |
collection | PubMed |
description | Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated with PDT undergo complete remission. The main cause of their failure is resistance to anticancer therapy. In many cancers, resistance to various anticancer treatments is correlated with increased activity of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1). Enhanced activity of drug pumps may also affect the effectiveness of therapy. To investigate whether multidrug resistance mechanisms underlie PDT resistance in VIN, porphyrins were isolated from sensitive and resistant vulvar cancer cells and their culture media. APE1 activity was measured, and survival assay after PDT combined with APE1 inhibitor was performed. Our results revealed that resistant cells accumulated and effluxed less porphyrins than sensitive cells, and in response to PDT, resistant cells increased APE1 activity. Moreover, PDT combined with inhibition of APE1 significantly decreased the survival of PDT-resistant cells. This means that resistance to PDT in vulvar cancer may be the result of alterations in the heme synthesis pathway. Moreover, increased APE1 activity may be essential for the repair of PDT-mediated DNA damage, and inhibition of APE1 activity may increase the efficacy of PDT. |
format | Online Article Text |
id | pubmed-9028356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90283562022-04-23 Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer Mossakowska, Beata Joanna Shahmoradi Ghahe, Somayeh Cysewski, Dominik Fabisiewicz, Anna Tudek, Barbara Siedlecki, Janusz Aleksander Int J Mol Sci Article Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated with PDT undergo complete remission. The main cause of their failure is resistance to anticancer therapy. In many cancers, resistance to various anticancer treatments is correlated with increased activity of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1). Enhanced activity of drug pumps may also affect the effectiveness of therapy. To investigate whether multidrug resistance mechanisms underlie PDT resistance in VIN, porphyrins were isolated from sensitive and resistant vulvar cancer cells and their culture media. APE1 activity was measured, and survival assay after PDT combined with APE1 inhibitor was performed. Our results revealed that resistant cells accumulated and effluxed less porphyrins than sensitive cells, and in response to PDT, resistant cells increased APE1 activity. Moreover, PDT combined with inhibition of APE1 significantly decreased the survival of PDT-resistant cells. This means that resistance to PDT in vulvar cancer may be the result of alterations in the heme synthesis pathway. Moreover, increased APE1 activity may be essential for the repair of PDT-mediated DNA damage, and inhibition of APE1 activity may increase the efficacy of PDT. MDPI 2022-04-08 /pmc/articles/PMC9028356/ /pubmed/35456936 http://dx.doi.org/10.3390/ijms23084117 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mossakowska, Beata Joanna Shahmoradi Ghahe, Somayeh Cysewski, Dominik Fabisiewicz, Anna Tudek, Barbara Siedlecki, Janusz Aleksander Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title | Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title_full | Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title_fullStr | Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title_full_unstemmed | Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title_short | Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer |
title_sort | mechanisms of resistance to photodynamic therapy (pdt) in vulvar cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028356/ https://www.ncbi.nlm.nih.gov/pubmed/35456936 http://dx.doi.org/10.3390/ijms23084117 |
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